Answer the following questions about the drug structures shown below.

1. Match the drug structures with their structural classification.

( 5 ) Amino acid derivative

( 2 ) Dibenzazepine

( 4 ) Hydantoin

( 1 ) Tricyclic benzodiazepine

( 3 ) Barbiturate

2. List those drugs, by number, that will form a pharmaceutically-useful salt with HCl.

Drug #1 and #5

3. those drugs, by number, that will form a pharmaceutically-useful salt with NaOH.

Drug #3 and #5

4. Match the drug structures with ONE of the following therapeutic uses (note: a therapeutic use may be used more than once).

( 1 ) Anxiolytic

( 3 ) Sedative/hypnotic

( 2,4 ) Anti-epileptic

( 5 ) Muscle relaxant

5. Show the reaction of drug #1 with aqueous acid (H₃O⁺).

6. Comment on the therapeutic significance of this reaction.

The tricyclic benzodiazepines, unlike the benzodiazepin-2-ones, are stable in aqueous acid therefore permitting formulation of aqueous parenteral dosage forms of these drugs.

7. Show the biotransformation of drug #2 (oxcarbazepine) to its active metabolite.

8. Explain the therapeutic advantage of oxcarbazaepine compared to its closely related analogue carbamazepine.

Oxcarbazepine is metabolized to a pharmacologically-active metabolite while carbamazepine is metabolized to a toxic metabolite.

9. Draw the structure of one CYP450 oxidase metabolite of drug #3. Explain how interactions between drug #3 and other drugs metabolized by the same enzyme system may occur.

Drug #3, a barbiturate derivative, is a potent inducer of hepatic oxidase drug metabolizing enzyme systems. Its use with other drugs metabolized by the same enzyme system can increase the usual clearance rate of these other drugs.

10. The duration of therapeutic action of drug #3 will likely be (check one answer):

( ) 1-4 hours

( X ) 4-12 hours

( ) 1-2 days

11. Draw the structure of two (2) different metabolites of drug #4 resulting from CYP450 oxidase biotransformation.

12. Describe how drug #4 is involved in competitive protein binding interactions with other drugs.

OND of drug #4 produces an acidic metabolite (N-H) that is highly protein bound (lipophilic anion) and can compete with other protein bound drugs for these sites.

13. Drug #5 has a relatively short duration of action. Explain why and show the structure of an analogue of drug #5 that will likely have a longer duration of action.

Short duration of action is related to rapid catabolism via CH₃ oxidation.

Drug #5 is a 3-arylGABA derivative having muscle relaxant properties. Replacement of the metabolically labile p-CH₃ group with metabolically-stable, lipophilic Cl should extend the metabolic half-life of the drug.

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